Unique cellular immune signatures of multisystem inflammatory syndrome in children.

The clinical presentation of MIS-C overlaps with other infectious/non-infectious diseases such as acute COVID-19, Kawasaki disease, acute dengue, enteric fever, and systemic lupus erythematosus. We examined the ex-vivo cellular parameters with the aim of distinguishing MIS-C from other syndromes with overlapping clinical presentations. MIS-C children differed from children with non-MIS-C conditions by having increased numbers of naïve CD8+ T cells, naïve, immature and atypical memory B cells and diminished numbers of transitional memory, stem cell memory, central and effector memory CD4+ and CD8+ T cells, classical, activated memory B and plasma cells and monocyte (intermediate and non-classical) and dendritic cell (plasmacytoid and myeloid) subsets. All of the above alterations were significantly reversed at 6-9 months post-recovery in MIS-C. Thus, MIS-C is characterized by a distinct cellular signature that distinguishes it from other syndromes with overlapping clinical presentations. Trial Registration: ClinicalTrials.gov clinicaltrial.gov. No: NCT04844242.

Impact of Critical Care Point-of-Care Ultrasound Short-Courses on Trainee Competence.

OBJECTIVES: Competence in point-of-care ultrasound is recommended/mandated by several critical care specialties. Although doctors commonly attend point-of-care ultrasound short-courses for introductory training, there is little follow-up data on whether they eventually attain competence. This study was done to determine the impact of point-of-care ultrasound short-courses on point-of-care ultrasound competence. DESIGN: Web-based survey. SETTING: Follow-up after point-of-care ultrasound short-courses in the Asia-Pacific region. SUBJECTS: Doctors who attended a point-of-care ultrasound short-course between December 2015 and February 2018. INTERVENTIONS: Each subject was emailed a questionnaire on or after 6 months following their short-course. They were asked if they had performed at least 30 structured point-of-care ultrasound scans and/or reached point-of-care ultrasound competence and their perceived reasons/challenges/barriers. They were also asked if they used point-of-care ultrasound as a clinical diagnostic aid. MEASUREMENTS AND MAIN RESULTS: The response rate was 74.9% (182/243). Among the 182 respondents, only 12 (6.6%) had attained competence in their chosen point-of-care ultrasound modality, attributing their success to self-motivation and time management. For the remaining doctors who did not attain competence (170/182, 93.4%), the common reasons were lack of time, change of priorities, and less commonly, difficulties in accessing an ultrasound machine/supervisor. Common suggestions to improve short-courses included requests for scanning practice on acutely ill ICU patients and prior information on the challenges regarding point-of-care ultrasound competence. Suggestions to improve competence pathways included regular supervision and protected learning time. All 12 credentialled doctors regularly used point-of-care ultrasound as a clinical diagnostic aid. Of the 170 noncredentialled doctors, 123 (72.4%) reported performing unsupervised point-of-care ultrasound for clinical management, either sporadically (42/170, 24.7%) or regularly (81/170, 47.7%). CONCLUSIONS: In this survey of doctors attending point-of-care ultrasound short-courses in Australasia, the majority of doctors did not attain competence. However, the practice of unsupervised point-of-care ultrasound use by noncredentialled doctors was common. Further research into effective strategies to improve point-of-care ultrasound competence is required.

Immune Profiles in Multisystem Inflammatory Syndrome in Children with Cardiovascular Abnormalities.

BACKGROUND: Multisystem inflammatory syndrome in children (MIS-C), a sequela of severe acute respiratory syndrome coronavirus-2 infection (SARS-CoV2), has been progressively reported worldwide, with cardiac involvement being a frequent presentation. Although the clinical and immunological characteristics of MIS-C with and without cardiac involvement have been described, the immunological differences between cardiac and non-cardiac MIS-C are not well understood. METHODS: The levels of type 1, type 2, type 17, other proinflammatory cytokines and CC chemokines and CXC chemokines were measured using the Magpix multiplex cytokine assay system in MIS-C children with MIS-C cardiac (MIS-C (C) (n = 88)) and MIS-C non-cardiac (MIS-C (NC) (n = 64)) abnormalities. RESULTS: MIS-C children with cardiac manifestations presented with significantly increased levels of cytokines such as IFN-γ, IL-2, TNFα, IL-5, IL-1α, IL-1ß, IL-6, IL-10 and IL-12p70 and chemokines such as CCL2, CCL3, CCL11 and CXCL10 in comparison to MIS-C children without cardiac manifestations. Clustering analysis revealed that cytokines and chemokines could clearly distinguish MIS-C children with and without cardiac manifestations. In addition, these responses significantly diminished and normalized 9 months after treatment. CONCLUSIONS: This is one of the first studies characterizing and differentiating systemic inflammation in MIS-C with and without cardiac involvement from a low- and middle-income country (LMIC). Our study contributes to the existing body of evidence and advances our knowledge of the immunopathogenesis of MIS-C in children.

Clinical profile of scrub typhus in children and its association with hemophagocytic lymphohistiocytosis.

OBJECTIVE: To study the clinical profile of children with scrub typhus and its association with hemophagocytic lymphohistiocytosis. METHODS: Children presenting with unexplained fever and multi-systemic involvement between May to December 2011 were tested for scrub typhus using IgM ELISA kits. Occurrence of Hemophagocytic lymphohistiocytosis in IgM positive cases of scrub typhus was studied. RESULTS: Of the 35 children with unexplained fever and multi-systemic involvement, 15 children (9 boys) tested positive for scrub typhus. Thrombocytopenia, hypoalbuminemia and raised hepatic transaminases were observed in all children. Out of seven children evaluated for hemophagocytic lymphohistiocytosis. 3 met the criteria for hemophagocytosis. Two children (one with hemophagocytic lymphohistiocytosis) died. CONCLUSIONS: Scrub typhus is a common cause of unexplained fever in children in northern India. Hemophagocytic lymphohistiocytosis can occasionally complicate scrub typhus in children.